Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations
Among the 307 patients with a molecular diagnosis of MgD, 55 (17.9%) were mutated in a gene associated with a genetic syndrome. Eight percent (n=25) of the patients with mutations carried the m.3243A>G variant associated with MIDD (Maternally inherited diabetes and deafness). At time of referral very little had reported hearing loss or any other element of the typical syndromic presentation. Six percent of the patients were mutated in HNF1B even though the typical extra-pancreatic features were not known at time of referral. Surprisingly the third most prominent etiology in these rare forms was the WFS1 gene accounting for 2.9% of the patients with pathogenic mutations (n=9). None of them depicted a Wolfram syndrome presentation even though some features were reported in 6/9 patients.
Restricting the analysis of certain genes to patients with the respective specific phenotypes would miss out those with partial presentations. These results therefore underlie the undisputable benefit of NGS strategies even though the situation implies cascade consequences both for the molecular biologist and the clinician.